Takeda and Zinfandel Pharmaceuticals Initiate Phase 3 TOMMORROW Trial of AD-4833 for the Delay of Onset of Mild Cognitive Impairment Due to Alzheimer's Disease in Subjects Selected Using a Genetic-Based Biomarker Risk Assignment Algorithm

OSAKA, Japan and DURHAM, N.C., Aug. 26, 2013 /PRNewswire/ -- Takeda Pharmaceutical Company Limited ("Takeda") and its partner, Zinfandel Pharmaceuticals, Inc. ("Zinfandel"), today announced the initiation of TOMMORROW, a global Phase 3 clinical trial investigating a genetic-based biomarker risk assignment algorithm (risk assignment algorithm) to predict risk of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) within a five year period and to evaluate the efficacy of the investigational low dose pioglitazone (designated AD-4833 for this use) in delaying the onset of MCI due to AD in cognitively normal individuals at high risk as determined by the risk assignment algorithm.

The risk assignment algorithm is comprised of apolipoprotein E (APOE) and TOMM40 genotypes and age. Age and APOE genotype have previously been shown to indicate elevated risk of AD. The addition of TOMM40 is hypothesized to further refine the risk determination.

"To date, there have been a number of avenues investigated with the goal of altering the course of Alzheimer's disease but results have been unsuccessful," said Allen Roses, M.D., Chief Executive Officer, Zinfandel. "This is why the TOMMORROW trial is important. The potential to identify an individual's risk for developing MCI due to AD warrants further investigation."

AD is a devastating disease and diagnoses are increasing as the world's population ages. Currently 35.6 million people worldwide are living with some form of dementia. Studies show that individuals with MCI are at an increased risk of developing AD or another dementia with conversion rates of approximately 15 percent per year.

"AD-4833 is a member of a class of drugs known as PPAR (peroxisome proliferator-activated receptor)-gamma agonists which available data show may have a beneficial role in delaying symptoms of MCI due to AD," noted Stephen Brannan, M.D., Central Nervous System Development Therapeutic Area Head, Takeda. "TOMMORROW is a significant study and represents a novel clinical milestone and trial for the Alzheimer's community as it evaluates pre-symptomatic patients."

About the TOMMORROW TrialThe TOMMORROW trial is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The trial will use a genetic–based biomarker risk assignment algorithm comprised of APOE and TOMM40 genotypes and age, which is being studied to determine the risk of individuals developing MCI due to AD within a five year period. Cognitively normal individuals assessed as low risk will be assigned to receive placebo. Cognitively normal individuals assessed as high risk will be assigned to AD-4833 or placebo. The study duration is approximately five years or the time needed to achieve 410 conversions to MCI due to AD in the high risk group. Approximately 5,800 cognitively normal individuals aged 65-83 at 50 centers worldwide will be randomized into the study. The study will recruit internationally from large, diverse, community-based populations.

The study has two objectives:

For the genetic-based biomarker risk assignment algorithm, the primary objective is to qualify the risk assignment algorithm for identification of subjects at high risk of developing MCI due to AD within the next five years. The primary endpoint for the risk assignment algorithm is time to diagnosis of MCI due to AD for placebo-treated, high-risk subjects versus placebo-treated, low-risk subjects.

For AD-4833, considered an investigational drug for this use, the primary objective is to evaluate the efficacy of AD-4833 versus placebo in delaying the onset of MCI due to AD in cognitively normal individuals assessed as high risk based on the risk assignment algorithm. The primary endpoint is time to diagnosis of MCI due to AD for AD-4833-treated subjects versus placebo-treated subjects in the high-risk stratum. Key secondary objectives are to evaluate the effect of AD-4833 versus placebo on the progression of cognitive decline and to compare the effects of AD-4833 versus placebo on functional decline and instrumental activities of daily living.

About Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD)AD is a degenerative brain disease characterized by a progressive decline in memory, thinking, comprehension, calculation, language, learning capacity and judgment sufficient to impair personal activities of daily living. In 2011, the U.S. National Institute on Aging (NIA) and the Alzheimer's Association (AA) convened an expert panel to update the diagnostic guidelines for AD and also to develop criteria to define MCI due to AD and facilitate consensus in the field. Studies show that individuals with MCI are at an increased risk of developing AD or another dementia with conversion rates of approximately 15 percent per year. Approximately 18 million Americans are currently suffering from AD, and the rate of occurrence doubles every five years for those between 65 and 85 years of age. In the 2010 World Alzheimer Report, Alzheimer's Disease International estimated that there are 35.6 million people living with dementia worldwide in 2010, increasing to 65.7 million by 2030 and 115.4 million by 2050.

About Takeda Pharmaceutical Company LimitedLocated in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.

About Zinfandel PharmaceuticalsZinfandel Pharmaceuticals, based in Durham, NC, is a privately held company dedicated to using pharmacogenetics to improve prediction of risk for Alzheimer's disease and thus facilitate the development of effective therapies.